This letter is written to clarify the status of the XMRV/MLV CFS/ME study I am coordinating at the request of the National Institutes of Health. Although frequently described as the Lipkin Study, it is in fact the Alter, Bateman, Klimas, Komaroff, Levine, Lo, Mikovits, Montoya, Peterson, Ruscetti, and Switzer study, designed by these 11 investigators to bring their best methods for case ascertainment and characterization and state-of-the-art molecular and serological diagnostic tools to address the question of whether a retrovirus is associated with disease. My role in conjunction with Mady Hornig and Bruce Levin at Columbia University is to ensure that the study represents an appropriately powered, definitive, representative sample of CFS/ME patients across the United States; to receive and distribute samples; and to assess results obtained in individual laboratories for consistency and evidence for or against an association between retroviral signal and disease. I use the term signal because any finding related to a retrovirus, whether infectious or noninfectious, genetic material, protein, or antibody, may provide insights into disease or allow development of diagnostic tests even if a causative relationship is not established. My condition on accepting this charge from the NIH and the clinical and laboratory investigators is that each participant agree to unconditionally accept group criteria for defining cases to be used in this study. Laboratory investigators were also required to unequivocally endorse their results at the conclusion of the study. Several months were required to develop clinical criteria for case and control definition and to complete approvals for human subject protection. We encountered additional delays when Dr. Mikovits could no longer pursue her work at the WPI. At that juncture, some parties suggested that the work proceed at WPI without her. However, in my judgment, the value of this study rests in its inclusion of the original investigators who reported the XMRV/MLV findings. Thus, I was grateful when we found a way to fully engage Dr. Mikovits. At the time of this writing we have collected and distributed for laboratory analysis samples from 123 CFS/ME patients and 88 matched control subjects. We intend to complete collection and analysis of samples from 150 patients and 150 controls in early 2012.

There is criticism in some quarters that this study is unnecessary given results obtained by other investigators with other samples. However, the participating clinical and laboratory investigators and our team at Columbia do not agree. We are fully committed to completing the work rapidly and rigorously. For those who continue to express concerns that this study is an inappropriate use of resources in a challenging fiscal environment, please be assured that more than 85% of the funding associated with this initiative is invested in patient recruitment and characterization and sample collection, archiving, and distribution. Thus, irrespective of study outcome there will be unprecedented opportunity to explore hypotheses other than that disease is due to XMRV or MLV infection.

http://cii.columbia.edu/blog.htm?cid=CalAzy
... more than 85% of the funding associated with this initiative is invested in patient recruitment and characterization and sample collection, archiving, and distribution. Thus, irrespective of study outcome there will be unprecedented opportunity to explore hypotheses other than that disease is due to XMRV or MLV infection.

Sincerely yours,

W. Ian Lipkin, MD
Director, Center for Infection and Immunity

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Can anyone explain what he's referring to?
Are extra blood samples being taken during this study, for the purpose of then being available for future studies?
Is the patient (and perhaps control) cohort for this study going to be integrated with the Chronic Fatigue Initiative's patient cohort?

This letter is written to clarify the status of the XMRV/MLV CFS/ME study I am coordinating at the request of the National Institutes of Health.

Although frequently described as the Lipkin Study, it is in fact the Alter, Bateman, Klimas, Komaroff, Levine, Lo, Mikovits, Montoya, Peterson, Ruscetti, and Switzer study, designed by these 11 investigators to bring their best methods for case ascertainment and characterization and state-of-the-art molecular and serological diagnostic tools to address the question of whether a retrovirus is associated with disease.

My role in conjunction with Mady Hornig and Bruce Levin at Columbia University is to ensure that the study represents an appropriately powered, definitive, representative sample of CFS/ME patients across the United States; to receive and distribute samples; and to assess results obtained in individual laboratories for consistency and evidence for or against an association between retroviral signal and disease.

I use the term signal because any finding related to a retrovirus, whether infectious or noninfectious, genetic material, protein, or antibody, may provide insights into disease or allow development of diagnostic tests even if a causative relationship is not established. My condition on accepting this charge from the NIH and the clinical and laboratory investigators is that each participant agree to unconditionally accept group criteria for defining cases to be used in this study.

Laboratory investigators were also required to unequivocally endorse their results at the conclusion of the study. Several months were required to develop clinical criteria for case and control definition and to complete approvals for human subject protection.

We encountered additional delays when Dr. Mikovits could no longer pursue her work at the WPI. At that juncture, some parties suggested that the work proceed at WPI without her. However, in my judgment, the value of this study rests in its inclusion of the original investigators who reported the XMRV/MLV findings.

Thus, I was grateful when we found a way to fully engage Dr. Mikovits. At the time of this writing we have collected and distributed for laboratory analysis samples from 123 CFS/ME patients and 88 matched control subjects. We intend to complete collection and analysis of samples from 150 patients and 150 controls in early 2012.

There is criticism in some quarters that this study is unnecessary given results obtained by other investigators with other samples. However, the participating clinical and laboratory investigators and our team at Columbia do not agree. We are fully committed to completing the work rapidly and rigorously.

For those who continue to express concerns that this study is an inappropriate use of resources in a challenging fiscal environment, please be assured that more than 85% of the funding associated with this initiative is invested in patient recruitment and characterization and sample collection, archiving, and distribution.

Thus, irrespective of study outcome there will be unprecedented opportunity to explore hypotheses other than that disease is due to XMRV or MLV infection.

Can anyone explain what he's referring to?
Are extra blood samples being taken during this study, for the purpose of then being available for future studies?
Is the patient (and perhaps control) cohort for this study going to be integrated with the Chronic Fatigue Initiative's patient cohort?

Click to expand...

Morning,

I believe there are two studies that he is facilitating/coordinating. And that yes those samples collected from patients for this XMRV/MLV study will perhaps be made available for at least his other study known as the Next Generation Sequencing study.

Or at least I refer to it as that given that there is very little information available concerning either study really. Not sure where the Chronic Fatigue Initiative comes into play to be honest.

For those who continue to express concerns that this study is an inappropriate use of resources in a challenging fiscal environment, please be assured that more than 85% of the funding associated with this initiative is invested in patient recruitment and characterization and sample collection, archiving, and distribution.

Thus, irrespective of study outcome there will be unprecedented opportunity to explore hypotheses other than that , MD
Director, Center for Infection and Immunity

All rather depending on the questions I suppose Mary. Will this study - can any study - be definitive? Can it finally lay to rest the claims made by Mikovits and supported (if only in part) by Ruscetti, and by others as to some 'retroviral' component?

I don't know. One can ask so many questions can't one? For me it will hopefully prove - again - that Mikovits et al. are unable to replicate the results of Lombardi et al. and that Alter/Lo similarly cannot replicate their paper I guess.

XMRV/MLVs and CFS/ME? Nope. I don't think so. Then again I am more intrigued and I suppose hopeful about the other (main?) study of Lipkin's.

I don't think that - following this XMRV/MLV study - the participants will be able to claim XMRV/MLVs have any role in CFS/ME. So in that it will prove an answer.

There will always be those who think that various components of any study could have been completed better. And we don't have access to much information about recruitment, cohort selection, methodology really do we?

Mikovits herself said - and I can retrieve the exact quote - in connection with this study that if they were wrong before then this will prove it.

Sorry am a bit 'clumsy' with my words/typing today. The above probably doesn't make much sense but hope you get the gist

Well, this clarified some points. So there was never one "Lipkin/Mikovits" and one "Lipkin Deep Sequencing" study, but instead "one" big study?

Do I interpret it correctly that Lipkin is collecting samples from all the participants patients, which will be distributed again to all participants? And every participant does its own test(s), like e.g. Klimas NK-cell function (or other) and Lipkin his deep sequencing (or whatever it is called) and Mikovits her "HGRV"?

If this is the case, and it should lead nowhere, then I don't know what else could. And with just a bit of luck, we will zoom past MS and Alzheimer and Parkinsons and all the other chronic diseases with unknown causes.

I will be sitting on the edge of my seat until they announce the results I hope we will have a lot to mull over!

Tony as I understand it - and there is confusion here - there are two studies but the samples from this XMRV/MLV study may well be used in the NGS study. There are several threads about it containing all the sources of information that we have gleaned thus far but I believe this is the case.

Mikovits herself said - and I can retrieve the exact quote - in connection with this study that if they were wrong before then this will prove it.

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I don't care which way the answer will go, but I want to have either a definitive "Mikovits can reliably find something in a properly blinded study" or a definitive "Mikovits is not able to reliably find something".

And I will go anyway the answer from that study points but I will give a very very hard time anybody who disputes the results with the usual conspirational BS. (If there was something wrong with this study, why does Mikovits participate?)

Can it finally lay to rest the claims made by Mikovits and supported (if only in part) by Ruscetti, and by others as to some 'retroviral' component?

[...]

For me it will hopefully prove - again - that Mikovits et al. are unable to replicate the results of Lombardi et al. and that Alter/Lo similarly cannot replicate their paper I guess.

Click to expand...

Why do you want this to happen (regarding your first question)? Why do you hope for this outcome? I know others want the opposite to happen and one could ask the same question there, of course. I agree that the evidence is against the involvement of XMRV/MRV, but shouldn't we try to be unbiased and just see where the results go? Instead of wishing for a certain result? I prefer not to have a retrovirus, if they can discover another, treatable cause, but i don't see why one would want that door to be shut so quickly. I think even after a negative Lipkin study people who believe there is a retrovirus involved should continue to pursue that lead, if they can find funding.

(If there was something wrong with this study, why does Mikovits participate?)

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I'm not into conspiracies much either, but i don't think she has much of a choice here. If she were not to participate that would be held against her for ever, i guess. I think she has to participate and if the result is negative and she still believes in XMRV/MRV, she will have to find another way to prove it. Or find a way to prove the Lipkin study was flawed.

Not sure where the Chronic Fatigue Initiative comes into play to be honest.

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Lipkin's NGS study is part of the CFI initiative: the CFI is funding the NGS study; the CFI's cohort is to be used in the NGS study.

This is from the CFI's website:
"Following cohort recruitment, creation of the bio-bank and population of the database, the pathogen discovery and pathogenesis study led by the Center for Infection and Immunity at Columbia University seeks to uncover novel viruses implicated in the disease by using techniques that allow up to 20 pathogens to be searched simultaneously."

Perhaps the preparatory stages of the Lipkin multi-centre XMRV/MLV study is simultaniously building the CFI cohort and biobank

Thanks. And yep it could be. It seems they have indeed gone to great lengths to define/process the cohorts for the XMRV/MLVs Study - though again we don't really know very much in terms of specifics and won't I suppose until the study is complete and published.

It would seem rather a waste to process 150 patients in that way and then only for the one study - so it would make sense perhaps to use whatever samples are obtained for other projects or to at least keep the cohort and the results of their testing together.

I wonder if the selection process might influence later defining criteria? Could they be used say in the CCC or ICCME perhaps? Hmmm... hadn't thought along those lines before.

It was a possible answer that some might like and/or expect. This study by Lipkin will I think answer the claims made in Lombardi et al and Lo et al as to XMRV/MLV association with CFS/ME. It can't - I don't think - do more than that.

They and the others will - by all accounts - be able to employ the methodology that they believe revealed this association to them in their papers that has thus far not been replicated by the other studies or even those studies that they themselves participated in etc.

In terms of this being the only large, multi-lab, fully financed, almost complete, and in full agreement with the participants study into this alleged association in town - then this does represent the last chance for Mikovits and others to demonstrate what they have thus far claimed to be reproducible.

'That will be the definitive answer, she said. If were wrong and we cant reproduce it, then well be wrong, and thats how science works.'

I don't 'want' the outcome to be 'negative' for this association Eric. I believe the matter is already settled. The papers are retracted. The papers were 'crap'. There was no association.

If this study of Lipkin's and/or the other one shows something else then it will be pursued and subjected to scrutiny and attempts to replicate the results as per the two papers we are talking about.

I am quite excited about Lipkin's other study to be honest. But if this one does reveal anything that is 'new' or supports anything that has been claimed, then fine. It too will be subjected to the process - though some might express scepticism if what is 'found' relates to XMRV or MLVs.

I think this 'Lipkin study' into XMRV/MLVs is likely to be far more reliable than either Lombardi or Lo. But then that is simply - as is all that I write - my opinion as a non-scientist.